Background/Aim: Epithelial to mesenchymal transition (EMT), and focal adhesion kinase (FAK) facilitate lung cancer cell motility and survival. We, therefore, investigated the antimigratory effect of 3,4-dihydroxy-5,4'-dimethoxybibenzyl (DS-1) on human lung cancer cells. Materials and Methods: Cell viability and proliferation were examined by the 3-[4,5dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay. Filopodia formation, migration, and anchorage-independent growth assays were performed to assess metastatic behaviors while EMT-related proteins, integrins, and FAK-RhoA pathway were evaluated by western blot analysis. Results: We found that DS-1 significantly inhibited the proliferation of lung cancer cells compared to the control. The aggressive behavior of cancer cells, including migration and invasion, was significantly reduced by DS-1. Anchorage-independent growth analysis provided evidence that DS-1 suppressed the growth and survival of cancer cells in detached conditions as indicated by the significant reduction in size and number of colonies. With regard to the mechanisms involved, we found that DS-1-suppressed EMT, as indicated by the reduction of EMT markers, namely Ncadherin, SNAIL and SLUG, and increased levels of the epithelial marker, E-cadherin. In addition, DS-1 was shown to reduce the level of integrin β1 protein and FAK activation. Conclusion: DS-1 suppressed lung cancer metastasis via suppressing EMT, integrin β1 expression and FAK-related signaling.Metastasis is the primary cause of cancer-related morbidity and mortality. Lung cancer is often diagnosed at a late stage with metastasis (1). Studies reported that 20-40% of advanced lung cancer patients develop brain metastases, which significantly reduces their quality of life (2, 3). Metastatic cancer cells resist therapy (4) and, due to their increased migration and invasion, actively spread, leading to the formation of secondary tumors (5).The change of cancer cell phenotype from epithelial into motile mesenchymal cells through the epithelial-mesenchymal transition (EMT) is essential for migration, invasion, and survival in detached conditions during metastasis (6, 7). The major hallmarks of this process are the loss of cell polarity, dissociation of cell-cell junctions, and restructuring of the extracellular matrix (8). Along with EMT progression, expression of motility-and adhesion-regulatory proteins is altered, including the switch from E-cadherin to N-cadherin (9, 10). N-Cadherin facilitates the interaction of cancer and stromal cells, facilitating cancer cell migration and invasion (8,11,12). Both E-cadherin and N-cadherin are adherens junction molecules (13). However, E-cadherin expression is exhibited in epithelial tissue and contributes to maintaining cell integrity and homeostasis. Expression of E-cadherin has been correlated with better prognosis and long-term overall survival in patients with lung cancer (11). In contrast, N-cadherin is mostly expressed in mesenchymal cells and is associated with cell motility (14). Thus, c...
Background/Aim: Cancer metastasis is the main cause of mortality in cancer patients. As lung cancer patients are mostly detected at metastatic stages, strategies that inhibit cancer metastasis may offer effective therapies. Activation of FAK and Akt/mTOR pathways promotes the highly metastatic phenotypes of epithelial to mesenchymal transition (EMT). We unraveled EMT inhibitory action of pongamol and the mechanism controlling cell dissemination in lung cancer cells. Materials and Methods: Cytotoxic and antiproliferative effects of pongamol were determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and necrosis induction in response to pongamol treatment was observed and visualized by nuclei staining assay. Wound healing migration, invasion, and anchorage-dependent growth assay were conducted to evaluate metastatic behaviors. EMT protein expression and FAK pathway were detected by western blot analysis. Results: Pongamol at 0-100 μM exhibited significant inhibition on migration, and invasion of cancer cells. Regarding anoikis resistance potential, the compound significantly inhibited survival and growth of cancer cells in an anchorageindependent manner, as indicated by the depletion of growing colonies in pongamol-pretreated cells. Protein level analysis further showed that pongamol exerted its anti-metastasis effect by inhibiting EMT, as indicated by a decrease of several mesenchymal proteins (N-cadherin, vimentin, Snail, and Slug). Regarding the up-stream mechanisms, we found that pongamol inhibited activation of FAK and Akt/mTOR signaling pathways. Conclusion: Pongamol exhibits potent anti-metastatic activity through suppressing key potentiating factors of cancer metastasis EMT and FAK.
Bidara plants have the efficacy as antioxidants, anti-inflammatory,antimicrobial, anti-fungal and prevents tumours. Bidara is efficacious to protecthuman DNA cells caused by damage from actinic radiation. This study aims toexplore the acute toxicity test of the ethanol extract of Bidara leaves using whitemice as experimental animals. A total of 30 white rats (Rattus norvegicus) Wistarstrain obtained from the Eureka Research Laboratory (Palembang, Indonesia)weighing between 200 - 250 grams. After one week of adaptation, the mice wererandomly divided into the following six groups, each containing five animals:Normal control group and Bidara extract group (50mg/kg BW; 150 mg/kg BW;450 mg/kg BW; 1350 mg/kg BW; and 4050 mg/kg BW). This study shows thatthe extract of Bidara leaves has a relatively high toxic dose, namely at a dose of4050 mg/kg BW. Bidara leaf extract at doses below 1500 mg/kg BW, shows notoxic effect on the liver. In conclusion, bidara leaf extract has a toxic dose above4000 mg/kg BW in Wistar white rats.
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